ANTIBIOTICS FROM GLIDING BACTERIA .50. CHEMICAL MODIFICATION OF SORANGICIN-A AND STRUCTURE-ACTIVITY RELATIONSHIP .2. DERIVATIVES OBTAINED BY REDUCTION, OXIDATION AND REARRANGEMENT REACTIONS

The synthesis of 38 derivatives of sorangicin A (1) with modifications of the three hydroxyl groups and the conjugated triene is described. By oxidation and reduction reactions 21-desoxy-21-oxo sorangicin (8), 21-epi-sorangicin (9) and 21-desoxysorangicins 14, 15 were obtained. With protection of the 21,22-diol the 24,25-didehydro-25-desoxysorangicin (18), 25-desoxy-25-oxosorangicins 21, 22 and 25-epi-sorangicins 23, 24 were prepared. Further, the 25-oxo derivatives 21, 22 were transformed into the oximes 25 - 28 and the 25-desoxy-25,25-difluoro sorangicin (31). Catalytic reduction of sorangicin A (1) gave the 37,43-dihydro derivative 35, thermolysis the cyclohexadienes 36, 37 and fluoride-induced isomerisation the 36,38,40-trienol ethers 38, 39. - Activities against Staphylococcus aureus, Escherichia coli, and in vitro inhibition of RNA polymerase of selected derivatives were examined. With most compounds a reduced biological activity was observed, some derivatives retained their activity (23 - 28, 31) and three were improved for certain strains (18, 21, 22) although they showed reduced enzyme inhibition activity.